Convection-Enhanced Delivery of 124I-8H9 for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Weill Medical College of Cornell University
Johns Hopkins University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01502917
First received: December 29, 2011
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to test the safety of a new method to treat Diffuse Intrinsic Pontine Glioma (DIPG). The researchers will use "convection-enhanced delivery" (CED) to deliver an agent called 124I-8H9. CED is performed during surgery. The study agent is infused through a small tube placed into the tumor in the brain. Many studies have shown this can safely be done in animals but this study is the first time 124I-8H9 will be given by CED in humans. This will be one of the first times that CED has been performed in the brain stem.

8H9 is something called an antibody. Antibodies are made by the body to fight infections and sometimes cancer. The antibody 8H9 is produced by mice and can attack many kinds of tumors. A radioactive substance, 124I, is attached to 8H9. 124I-8H9 sticks to parts of tumor cells and can cause the tumor cells to die from radiation. Studies have also been done on humans using 124I-8H9 to treat other kinds of cancer. Our studies of some DPG and related tumors suggest that 8H9 will bind to the tumor, but the investigators don't know that for sure.

In this study, the researchers want to find out how safe 124I-8H9 given by CED is at different dose levels. They will look to see what effects (both good and bad) it has on the patient. The dose of 124I-8H9 will increase for each new group of patients. The procedure has already been safely performed with lower doses and infusion volumes in a number of patients here at MSKCC. The amount they get will depend on when they enter the study. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some more patients may be treated with a lower dose to make sure that dose is safe.


Condition Intervention Phase
Brain Cancer
Brain Stem Glioma
Radiation: Radioactive iodine-labeled monoclonal antibody 8H9
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Convection-Enhanced Delivery of 124I-8H9 for Patients With Non-Progressive Diffuse Pontine Gliomas Previously Treated With External Beam Radiation Therapy

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Determination that a dose is safe will be made following the treatment of at least 3 but no more than 6 patients at a particular dose level. The dose levels are DL1 (0.25 mCi), DL2 (0.5 mCi), DL3 (0.75 mCi), DL4 (1 mCi) and fallback DL0 (0.125 mCi). An incidence of dose-limiting toxicity (DLT) in the range of 25% is considered acceptable in this population.

  • safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Adverse events (toxicity) will be assessed and classified according to the Clinical Terminology Criteria for Adverse Events version 4.0 (CTCAE). Generally, grade 3 toxicities interfere with activities of daily living (ADLs) and grade 4 toxicities are life-threatening. Grade 5 toxicities cause death.


Secondary Outcome Measures:
  • overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall survival from the time of diagnosis will be recorded for every patient in this study. Overall survival will be estimated by Kaplan-Meier methodology.


Estimated Enrollment: 48
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radioactive iodine-labeled monoclonal antibody 8H9
This is a therapeutic Phase I study intended to assess the safety of convection-enhanced delivery (CED) of radioimmunotherapy in the treatment of children with diffuse pontine glioma.
Radiation: Radioactive iodine-labeled monoclonal antibody 8H9
Prior to treatment, children will be pre-medicated with super-saturated potassium iodide (SSKI) and liothyronine to prevent thyroid uptake of the therapeutic radioisotopes. The proposed intervention is a surgical procedure using interstitial infusion of the radiolabeled monoclonal antibody 124I-8H9 into the brain stem tumor. This will be performed by stereotactic placement of a small caliber infusion cannula into the tumor followed by a slow infusion (CED) of 124I-8H9. Following treatment, these children will be monitored during inpatient hospitalization with clinical evaluations and PET/CT scans of the brain and other organs. Clinical observations, intensive care unit monitoring, routine blood and interval imaging studies (MRI and PET/CT scans) will be performed at predetermined time points.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Consensus of diagnosis must be reached by a multidisciplinary pediatric neuro-oncology team by considering both clinical evidence and MRI presentation. Tissue diagnosis is not required.
  • The patient must have undergone prior external beam radiotherapy to a dose of 54-60 Gy to the brain stem. At least 4 weeks but no more than 14 weeks must have elapsed from the completion of radiotherapy.
  • The patient must be in adequate general condition for study, with Lansky or Karnofsky Performance Score of > or = to 50 at study entry .

Lansky Performance scale will be used for patients ≤16 years of age.

  • The patient must be > to or = to 3 and ≤ 21 years old.
  • Patient must weigh a minimum of 8 kg.

Exclusion Criteria:

  • Clinical and/or radiographic (MRI) progression of tumor following external beam radiation therapy.
  • Metastatic disease.
  • Untreated symptomatic hydrocephalus determined by treating physician.
  • AST or ALT > 2x the upper limit of normal.
  • Platelets < 100,000/mcL.
  • ANC < 1000/mcL.
  • Abnormal PT (Inr) >1.5 INR or PTT > 42 sec (may be corrected with FFP, cryoprecipitate, vitamin K, etc).
  • Total bilirubin > 2.0 mg/dl.
  • Serum creatinine > 1.5x the upper limit of normal for age, or calculated creatinine clearance or nuclear GFR < 70 ml/min/1.73 m2.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502917

Contacts
Contact: Mark Souweidane, MD 212-639-2336
Contact: Ira Dunkel, MD 212-639-2336

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Maria Donzelli, PNP    212-639-2336      
Principal Investigator: Mark Souweidane, MD         
Weill Medical College of Cornell University Not yet recruiting
New York, New York, United States, 10021
Contact: Maria Donzelli, PNP    212-639-2336      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Weill Medical College of Cornell University
Johns Hopkins University
Investigators
Principal Investigator: Mark Souweidane, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01502917     History of Changes
Other Study ID Numbers: 11-011
Study First Received: December 29, 2011
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Brain stem glioma
CNS
MAB 124I-8H9
infusion cannula
DIPG
Diffuse Intrinsic Pontine Glioma
11-011

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Pontine Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Astrocytoma
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Iodine
N-(2-aminoethyl)-5-isoquinolinesulfonamide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Trace Elements
Micronutrients

ClinicalTrials.gov processed this record on July 24, 2014